Russell Rosenberg1, Michael J Thorpy2, Yves Dauvilliers3, Paula K Schweitzer4, Gary Zammit5,6, Mark Gotfried7, Shay Bujanover8, Brian Scheckner9, Atul Malhotra10. 1. NeuroTrials Research, Inc, Atlanta, Georgia. 2. Montefiore Medical Center, Bronx, New York. 3. Sleep Unit, Department of Neurology, Gui-de-Chauliac Hospital, CHU Montpellier, INSERM, Montpellier, France. 4. Sleep Medicine and Research Center, St Luke's Hospital, Chesterfield, Missouri. 5. Clinilabs Drug Development Corporation, New York, New York. 6. Icahn School of Medicine at Mount Sinai, New York, New York. 7. Pulmonary Associates, PA, Phoenix, Arizona. 8. Jazz Pharmaceuticals, Palo Alto, California. 9. Jazz Pharmaceuticals, Philadelphia, Pennsylvania. 10. University of California, San Diego, San Diego, California.
Abstract
STUDY OBJECTIVES: This post hoc analysis characterized the weekly incidence and overall duration of common early-onset, treatment-emergent adverse events (TEAEs) during solriamfetol treatment. METHODS: Participants (obstructive sleep apnea [OSA], n = 474; narcolepsy, n = 236) were randomized to 12 weeks of placebo or solriamfetol 37.5 (OSA only), 75, 150, or 300 mg. For common early-onset TEAEs (those occurring in ≥ 5% of participants in any solriamfetol dose group and with a higher incidence than that observed in placebo-treated participants during week 1), the incidence of new occurrence or change in severity over time was calculated for each subsequent study week. Data were analyzed separately for each study and summarized by placebo and combined solriamfetol groups. RESULTS: Common early-onset TEAEs (at doses ≤ 150 mg; ie, approved doses) included headache (OSA, 5.1%; narcolepsy, 8.5%), nausea (OSA, 2.5%; narcolepsy, 4.2%), decreased appetite (OSA, 4.2%; narcolepsy, 5.9%), as well as anxiety (2.1%), insomnia (1.3%), and feeling jittery (3.0%) in OSA and dry mouth (4.2%) in narcolepsy. Incidence of common early-onset TEAEs was highest at week 1 and decreased over time. In OSA at doses ≤ 150 mg, headache, nausea, and feeling jittery had median durations ≤ 8 days, whereas decreased appetite, anxiety, and insomnia had longer durations. In narcolepsy at doses ≤ 150 mg, headache and nausea had median durations ≤ 8 days, whereas decreased appetite and dry mouth had longer durations. Most TEAEs were mild to moderate in severity. CONCLUSIONS: Common early-onset TEAEs with solriamfetol are limited in duration, with the majority subsiding during the first week of treatment. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Twelve-week Study of the Safety and Efficacy of JZP-110 in the Treatment of Excessive Sleepiness in Narcolepsy; URL: https://clinicaltrials.gov/ct2/show/NCT02348593; Identifier: NCT02348593; and Name: Twelve-week Study of the Safety and Efficacy of JZP-110 in the Treatment of Excessive Sleepiness in OSA; URL: https://clinicaltrials.gov/ct2/show/NCT02348606; Identifier: NCT02348606. CITATION: Rosenberg R, Thorpy MJ, Dauvilliers Y, et al. Incidence and duration of common early-onset adverse events in randomized controlled trials of solriamfetol for treatment of excessive daytime sleepiness in obstructive sleep apnea and narcolepsy. J Clin Sleep Med. 2022;18(1):235-244.
STUDY OBJECTIVES: This post hoc analysis characterized the weekly incidence and overall duration of common early-onset, treatment-emergent adverse events (TEAEs) during solriamfetol treatment. METHODS: Participants (obstructive sleep apnea [OSA], n = 474; narcolepsy, n = 236) were randomized to 12 weeks of placebo or solriamfetol 37.5 (OSA only), 75, 150, or 300 mg. For common early-onset TEAEs (those occurring in ≥ 5% of participants in any solriamfetol dose group and with a higher incidence than that observed in placebo-treated participants during week 1), the incidence of new occurrence or change in severity over time was calculated for each subsequent study week. Data were analyzed separately for each study and summarized by placebo and combined solriamfetol groups. RESULTS: Common early-onset TEAEs (at doses ≤ 150 mg; ie, approved doses) included headache (OSA, 5.1%; narcolepsy, 8.5%), nausea (OSA, 2.5%; narcolepsy, 4.2%), decreased appetite (OSA, 4.2%; narcolepsy, 5.9%), as well as anxiety (2.1%), insomnia (1.3%), and feeling jittery (3.0%) in OSA and dry mouth (4.2%) in narcolepsy. Incidence of common early-onset TEAEs was highest at week 1 and decreased over time. In OSA at doses ≤ 150 mg, headache, nausea, and feeling jittery had median durations ≤ 8 days, whereas decreased appetite, anxiety, and insomnia had longer durations. In narcolepsy at doses ≤ 150 mg, headache and nausea had median durations ≤ 8 days, whereas decreased appetite and dry mouth had longer durations. Most TEAEs were mild to moderate in severity. CONCLUSIONS: Common early-onset TEAEs with solriamfetol are limited in duration, with the majority subsiding during the first week of treatment. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Twelve-week Study of the Safety and Efficacy of JZP-110 in the Treatment of Excessive Sleepiness in Narcolepsy; URL: https://clinicaltrials.gov/ct2/show/NCT02348593; Identifier: NCT02348593; and Name: Twelve-week Study of the Safety and Efficacy of JZP-110 in the Treatment of Excessive Sleepiness in OSA; URL: https://clinicaltrials.gov/ct2/show/NCT02348606; Identifier: NCT02348606. CITATION: Rosenberg R, Thorpy MJ, Dauvilliers Y, et al. Incidence and duration of common early-onset adverse events in randomized controlled trials of solriamfetol for treatment of excessive daytime sleepiness in obstructive sleep apnea and narcolepsy. J Clin Sleep Med. 2022;18(1):235-244.
Authors: Karel Sonka; David Kemlink; Jitka Busková; Martin Pretl; Zuzana Srůtková; Eszter Maurovich Horvat; Pavel Vodicka; Veronika Poláková; Sona Nevsímalová Journal: Neuro Endocrinol Lett Date: 2010 Impact factor: 0.765
Authors: Carl Stepnowsky; Kathleen F Sarmiento; Shay Bujanover; Kathleen F Villa; Vicky W Li; Natalia M Flores Journal: J Clin Sleep Med Date: 2019-02-15 Impact factor: 4.062
Authors: Susheel P Patil; Indu A Ayappa; Sean M Caples; R Joh Kimoff; Sanjay R Patel; Christopher G Harrod Journal: J Clin Sleep Med Date: 2019-02-15 Impact factor: 4.062
Authors: J-L Pépin; V Viot-Blanc; P Escourrou; J-L Racineux; M Sapene; P Lévy; B Dervaux; X Lenne; A Mallart Journal: Eur Respir J Date: 2009-05 Impact factor: 16.671
Authors: Terri E Weaver; Greg Maislin; David F Dinges; Thomas Bloxham; Charles F P George; Harly Greenberg; Gihan Kader; Mark Mahowald; Joel Younger; Allan I Pack Journal: Sleep Date: 2007-06 Impact factor: 5.849